P566: RESULTS OF NON-CHEMOTERAPEUTIC TREATMENT OF PATIENTS WITH DE NOVO ACUTE PROMYELOCYTIC LEUKEMIA
Authors: Vera Troitskaya, Arina Semenova, Zalina Fidarova, Andrey Sokolov, Irina Lukyanova, Olga Aleshina, Gennady Galstyan, Elena Gribanova, Elena Lukina, Valentina Dvirnyk, Tatyana Obukhova, Andrey Sudarikov, Sergey Kulikov, Elena Parovichnikova
Journal: HemaSphere (2023)

Background: The use of non-chemotherapeutic methods with arsenic trioxide (ATO) and tretinoin (ATRA) for the treatment of acute promyelocytic leukemia (APL) allows achieving remission in more than 90% of patients with de novo APL with less toxicity compared to chemotherapy treatment. However, early mortality remains high in patients with initial leukocytosis more than 10×109/l. Aims: To evaluate the efficacy and toxicity of the ATRA+ATO protocol in patients with de novo APL. Methods: From 2016 to 2022, 79 patients with de novo APL aged 19–78 years (Me – 44) were included in the ATRA+ATO research protocol at the National Research Center for Hematology, M/F — 32/47. According to ELN classification, 71% of patients (n=56) were assigned to the low risk group, and 29% (n=23) were assigned to the high-risk group. Patients completed 1 induction course of 30–60 days (ATO 0.15 mg/kg IV + ATRA 45 mg/m2 PO) until morphological remission achieving in the low risk group, and 60 days in the high risk group and consolidation courses (4 for low risk and 5 for high risk). Patients from the high-risk group got idarubicin 8–12 mg/m2 (1–3 administrations) at the beginning of the induction course for cytoreduction, and patients with clinically significant hyperleukocytosis got cytarabine 100 mg/m2 (1–3 administrations). Results: The induction course was completed in 74 patients (93.7%). Of these, molecular remission was achieved in 73 (98.6%): after the introduction in 62 (84.9%), after the 1st course of consolidation in 10 (13.7%), after 2nd course of consolidation in 1 (1.4%). Early mortality was 6.3% (n=5), death in remission was 1.7% (n=1). All lethal cases were detected in patients from the high-risk group. A 0.83-114 times (median - 7) transient leukocytosis increasion was detected in 68/79 (86%) patients, 7 patients got cytarabine for cytoreduction, ATO was temporarily discontined in 2 patients. Differential syndrome was diagnosed in 26.6% of patients (n=21) on 1–20 (median – 2) day of induction therapy, ATO was temporarily discontinued in 2 patients of them. Infections were observed in 87.3% (n=69) of patients. 14 patients (17.7%) were transferred to the intensive care unit. Signs of cardiac toxicity of therapy were observed in 27.8% of patients (n=22) (QTc prolongation in 20 patients, excitation of the driver’s rhythm - 1, inversion of the T-wave - 1), hepatotoxicity gr. 3-4 — 31.6% (n=25), pancreatitis — 16.5% (n=13). After achieving remission, therapy was continued in an outpatient hospital. Currently, 73 patients (92.4%) are alive, the follow-up period is 0.03–57.7 months (median — 16.7 months), no cases of relapse were observed. 3-year OS in all patients was 92.3%, in the high-risk group – 100%, in the high-risk group – 73%. DFS is 99%. Summary/Conclusion: Risk-adapted strategy for non-chemotherapeutic treatment of acute promyelocytic leukemia based on combination of tretinon and arsinic trioxide allows to achieve 99.0% 3-year disease-free survival in patients as from the low-risk group as from the high-risk group. The main reason for unsuccessful therapy according to the ATO+ATRA protocol was early mortality in patients from the high-risk group.Keywords: ALL-trans retinoic acid (ATRA), Acute promyelocytic leukemia, Arsenic trioxide